IMIPRAMINE HCL, IMIPRAMINE PAMOATE

Chemistry - A tricyclic antidepressant agent, imipramine is available commercially in either thehydrochloride or pamoate salts. Imipramine HCl occurs as an odorless or practically odorless, white to off-white crystalline powder that is freely soluble in water or alcohol. Imipramine pamoateoccurs as a fine yellow powder that is practically insoluble water, but soluble in alcohol. The HClinjection has a pH of 4-5.

Storage, Stability, Compatibility

Imipramine HCl tablets and the pamoate capsules should bestored in tight, light resistant containers, preferably at room temperature. The HCl injection shouldbe stored at temperatures less than 40°C and freezing should be avoided. Expiration dates for oral
HCL products are from 3-5 years after manufacture and for the pamoate, 3 years followingmanufacture.
Imipramine HCl will turn yellow to reddish on exposure. Slight discoloration will not affectpotency, but marked changes in color are associated with a loss of potency. If small crystals arenoted in the injection solution, they may be resolubolized by immersing the ampule in hot water andagitating.

Pharmacology - IMIPRAMINE HCL, IMIPRAMINE PAMOATE

Imipramine and its active metabolite, desipramine, have a complicated pharmacologic profile. From a slightly oversimplified viewpoint, they have 3 main characteristics: blockage of the amine pump, thereby increasing neurotransmitter levels (principally serotonin, but also norepinephrine), sedation, and central and peripheral anticholinergic activity. While not completely understood, the antienuretic activity of imipramine is thought to be related to its anticholinergic effects. In animals, tricyclic antidepressants are similar to the actions of phenothiazines in altering avoidance behaviors.
Uses, Indications - In dogs, imipramine has been used to treat cataplexy and urinary incontinence.
In horses, imipramine has been used to treat narcolepsy and ejaculatory dysfunction.

Pharmacokinetics - IMIPRAMINE HCL, IMIPRAMINE PAMOATE

Imipramine is rapidly absorbed from both the GI tract and from parenteralinjection sites. Peak levels occur within 1-2 hours after oral dosing. Imipramine and desipramineenter the CNS and maternal milk in levels equal to that found in maternal serum. The drug ismetabolized in the liver to several metabolites, including desipramine, which is active. In humans theterminal half life is approximately 8-16 hours.

Contraindications, Precautions, Reproductive Safety

These agents are contraindicated if priorsensitivity has been noted with any other tricyclic. Concomitant use with monoamine oxidaseinhibitors is generally contraindicated. Isolated reports of limb reduction abnormalities have beennoted; restrict use to pregnant animals when the benefits clearly outweigh the risks.

Adverse Effects, Warnings

While there is little experience with this drug in domestic animals, the most predominant adverse effects seen with the tricyclics are related to their sedating and anticholinergic properties. However, adverse effects can run the entire gamut of systems, includinghematologic (bone marrow suppression), GI (diarrhea, vomiting), endocrine, etc. Refer to otherhuman references for additional information.
Overdosage, Acute Toxicity - Overdosage with tricyclics can be life-threatening (arrhythmias, cardiorespiratory collapse). Because the toxicities and therapies for treatment are complicated andcontroversial, it is recommended to contact a poison control center for further information in anypotential overdose situation.

Drug Interactions

Because of additive effects, use imipramine cautiously with other agents withanticholinergic or CNS depressant (including barbiturates and phenothiazines) effects. Tricyclicantidepressants used with antithyroid agents may increase the potential risk of agranulocytosis.
Cimetidine may inhibit tricyclic antidepressant metabolism and increase the risk of toxicity. Usein combination with sympathomimetic agents may increase the risk of cardiac effects(arrhythmias, hypertension, hyperpyrexia). Concomitant use with monoamine oxidase inhibitorsis generally contraindicated.
Laboratory Considerations - Tricyclics can widen QRS complexes, prolong PR intervals andinvert or flatten T-waves on ECG. Tricyclics may alter (increase or decrease) blood glucose levels.